What is the Optimal Triple Anti-platelet Therapy Duration in Patients with Acute Myocardial Infarction Undergoing Drug-eluting Stents Implantation?

Transcription

1 What is the Optimal Triple Anti-platelet Therapy Duration in Patients with Acute Myocardial Infarction Undergoing Drug-eluting Stents Implantation? Keun-Ho Park, Myung Ho Jeong, Min Goo Lee, Jum Suk Ko, Doo Sun Sim, Nam Sik Yoon, Hyun Ju Yoon, Hyung Wook Park, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Jeong Gwan Cho, Jong Chun Park, Jung Chaee kang

2 DES in AMI The culprit lesion: Less plaque volume and more thrombus

3 Pattern of healing at AMI culprit/vulnerable sites vs. Stable plaque following DES deployment Ruptured plaque vs. Fibroatheroma with thick fibrous cap Nakazawa G. et al. Circulation 2008;118:

4 Duration of Thienopyridine Tx Modified Recommendation The duration of thienopyridine therapy should be as follows: I IIa IIb III a. In patients receiving a stent (BMS or DES) during PCI for ACS, clopidogrel 75 mg daily or prasugrel 10 mg daily should be given for at least 12 months; I IIa IIb III b. If the risk of morbidity from bleeding outweighs the anticipated benefit afforded by thienopyridine therapy, earlier discontinuation should be considered ACC/AHA STEMI Guidelines

5 Anti-platelet Agents Anti-platelet effect Anti-proliferative effect Improvement in lipid metabolism Jackson SP. Nat Rev Drug Discov 2003;2:

6

7 Backgrounds (I)

8 Backgrounds (II)

9 What is the Optimal Triple Anti-platelet Therapy Duration in Patients with Acute Myocardial Infarction Undergoing Drug-eluting Stents Implantation? 1-month vs. 6-month? Longer duration, better outcomes?

10 Purpose Triple antiplatelet Tx after PCI using DES for AMI in Single Center (CNUH) Duration of Triple Antiplatelet Tx Group I (< 1 M) Group II (1-3 M) Group III (3-6 M) Group IV ( 6 M) Compared 1-year clinical outcomes

11 Selection of patients Methods : AMI patients received triple antiplatelet therapy after DES implantation selected from CNUH data base (n= 716, Nov May 2008) : Inclusion criteria AMI including STEMI and NSTEMI a combination of two of three characteristics : typical symptoms : elevated cardiac enzyme : typical ECG pattern Successful PCI using only DES : restoration of TIMI flow 3 with residual stenosis of <30% : Exclusion criteria Patients who had suffered MACE for 3 M after index procedure Triple Antiplatelet therapy (TA) : aspirin 100mg qd and clopidogrel 75mg qd plus cilostazol 100mg bid after PCI

12 Primary End-point (MACE) Definition : the composite of cardiac death, non-fatal AMI, stent thrombosis (ST) and Target vessel revascularization (TVR) Safety End-point : the composite of cardiac death, non-fatal AMI and ST Bleeding by TIMI investigators TIMI major bleeding : intracranial hemorrhage or bleeding with Hb dec. of >5g/dl or Hct dec. of >15% TIMI minor bleeding : a Hb dec. of >3g/dl or a Hct dec. >10%; if no site is found, then it is defined as a Hb dec. of >4 g/dl or Hct dec. of >12% TIMI minimal bleeding : any clinically overt sign of hemorrhage that is associated with a Hb dec. of <3g/dl or a Hct dec. of <9% Stent thrombosis (ARC definition as definite ST) : the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion.

13 Baseline Clinical Characteristics (I) Group I (n=265) Group II (n=232) Group III (n=86) Group IV (n=133) p-value Age, years 62.18± ± ± ± Male gender (%) 197 (74.3) 160 (69.0) 72 (83.7) 103 (77.4) Hypertension (%) 116 (43.8) 109 (47.0) 43 (50.0) 56 (60.2) Diabetes (%) 59 (22.3) 77 (33.2) 27 (31.4) 49 (39.4) Dyslipidemia (%) 10 (3.8) 10 (4.3) 5 (5.8) 4 (3.0) Smoking Hx (%) 176 (66.4) 138 (59.5) 60 (69.8) 94 (70.7) Current smoker (%) 126 (47.5) 91 (39.2) 41 (47.7) 72 (54.1) Ex-smoker (%) 50 (18.9) 47 (20.3) 19 (22.1) 22 (16.5) Family Hx (%) 13 (4.9) 11 (4.7) 6 (7.0) 4 (3.0) IHD Hx (%) 32 (12.1) 21 (9.1) 15 (17.4) 18 (13.5) Diagnosed ST elevation MI (%) 167 (63.0) 164 (70.7) 61 (70.9) 95 (71.4) Diagnosed Non-ST elevation MI (%) 98 (37.0) 68 (29.3) 25 (29.1) 38 (28.6) Mean duration of Triple Tx, days 18.15± ± ± ±75.38 <0.001

14 Baseline Clinical Characteristics (II) Group I (n=265) Group II (n=232) Group III (n=86) Group IV (n=133) p-value Killip class at admission (%) I 223 (84.1) 186 (80.2) 74 (86.0) 113 (84.9) II 23 (8.7) 19 (8.2) 5 (5.8) 10 (7.5) III 15 (5.7) 19 (8.2) 3 (3.5) 5 (3.8) IV 4 (1.5) 8 (3.4) 4 (4.7) 5 (3.8) LV ejection fraction, % 56.27± ± ± ± LV ejection fraction <50% (%) 68 (26.3) 69 (30.1) 18 (22.5) 36 (36.1) Creatinine clearance, ml/min 72.61± ± ± ± CKD (Ccr<60) 90 (34.4) 86 (37.1) 34 (40.5) 36 (27.1) Chronic kidney disease (%) Stage 1 64 (24.4) 44 (19.0) 21 (25.0) 43 (32.3) Stage (41.2) 102 (44.0) 29 (34.5) 54 (40.6) Stage 3 79 (30.2) 73 (31.5) 28 (33.3) 29 (21.8) Stage 4 7 (2.7) 11 (4.7) 6 (7.1) 4 (3.0) Stage 5 4 (1.5) 2 (0.9) 0 (0.0) 3 (2.3)

15 Angiographic Characteristics Group I (n=265) Group II (n=232) Group III (n=86) Group IV (n=133) p-value Infarct-related artery (%) LAD 141 (53.2) 121 (52.1) 38 (44.2) 78 (58.7) LCX 33 (12.5) 38 (16.4) 13 (15.1) 14 (10.5) RCA 84 (31.7) 68 (29.3) 33 (38.4) 39 (29.3) LM 7 (2.6) 5 (2.2) 2 (2.3) 2 (1.5) Diseased vessels (%) Single vessel 133 (50.2) 109 (47.0) 40 (46.5) 67 (50.4) Two vessel 77 (29.1) 64 (27.6) 23 (26.8) 36 (27.0) Three vessel 39 (14.7) 44 (18.9) 18 (20.9) 21 (15.8) LM disease 16 (6.0) 15 (6.5) 5 (5.8) 9 (6.8) ACC/AHA classification (%) Type A or B1 85 (32.1) 68 (29.3) 27 (31.4) 41 (30.8) Type B2 or C 180 (67.9) 164 (70.7) 59 (68.6) 92 (69.2) Preprocedural TIMI flow grade (%) (41.9) 91 (39.2) 38 (44.2) 60 (45.1) I 13 (4.9) 9 (3.9) 4 (4.7) 10 (7.5) II 69 (26.0) 62 (26.7) 28 (32.6) 29 (21.8) III 72 (27.2) 70 (30.2) 16 (18.6) 34 (25.6) 0.220

16 Procedural Characteristics Group I (n=265) Group II (n=232) Group III (n=86) Group IV (n=133) p-value Postprocedural TIMI flow grade (%) (0.4) 1 (0.4) 0 (0.0) 0 (0.0) I 0 (0.0) 0 (0.0) 1 (1.2) 0 (0.0) II 6 (2.3) 3 (1.3) 0 (0.0) 2 (1.5) III 258 (97.3) 228 (98.3) 85 (98.8) 131 (98.5) Use of Gp IIb/IIIa inhibitor 102 (38.5) 73 (31.5) 28 (30.4) 50 (37.6) Type of stent used (%) TAXUS 187 (70.6) 167 (72.0) 72 (83.7) 101 (75.9) Cypher 46 (17.4) 36 (15.5) 8 (9.3) 24 (18.0) Endeavor 32 (12.1) 29 (12.5) 6 (7.0) 8 (6.0) Stent diameter at target lesion, mm 3.23± ± ± ± Stent length at target lesion, mm 25.25± ± ± ± Total number of stents 1.71± ± ± ±

17 12-month Clinical Outcomes Group I (n=265) Group II (n=232) Group III (n=86) Group IV (n=133) p-value 12-month outcomes (%) Mortality 10 (3.8) 9 (3.9) 1 (1.2) 1 (0.8) Cardiac death 7 (2.7) 8 (3.5) 1 (1.2) 1 (0.8) Non-cardiac death 3 (1.1) 1 (0.4) 0 (0.0) 0 (0.0) Non-fatal MI 1 (0.4) 3 (1.3) 0 (0.0) 0 (0.0) Repeat PCI 24 (9.1) 33 (14.2) 10 (11.6) 12 (9.0) TLR 16 (6.0) 19 (8.2) 4 (4.6) 7 (5.3) TVR 16 (6.0) 21 (9.1) 4 (4.6) 7 (5.3) Non-target vessel revascularization 8 (3.1) 13 (5.6) 6 (7.0) 6 (4.5) Stent thrombosis, definite 1 (0.4) 3 (1.3) 1 (1.2) 0 (0.0) CVA 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) CABG 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Safety end-point 8 (3.0) 11 (4.7) 1 (1.2) 1 (0.8) Primary end-point 24 (9.1) 29 (12.5) 5 (5.8) 8 (6.0) 0.121

18 Baseline Clinical Chracteristics according to DTPA of 3-month (I) Duration of less than 3 months (n=497) Duration of more than 3 months (n=219) p-value Age, years 62.64± ± Male gender (%) 357 (71.8) 175 (79.9) Hypertension (%) 225 (45.3) 99 (45.2) Diabetes (%) 136 (27.4) 76 (34.7) Dyslipidemia (%) 20 (4.0) 9 (4.1) Smoking Hx (%) 314 (63.2) 154 (70.3) Current smoker (%) 217 (43.7) 113 (51.6) Ex-smoker (%) 97 (19.5) 41 (18.7) Family Hx (%) 24 (4.8) 10 (4.6) IHD Hx (%) 53 (10.7) 33 (15.1) Diagnosed ST elevation MI (%) 331 (66.6) 156 (71.2) Diagnosed Non-ST elevation MI (%) 166 (33.4) 63 (28.8) Mean duration of Triple Tx, days 34.10± ± <0.001

19 Baseline Clinical Chracteristics of according to DTPA of 3-month (II) Duration of less than 3 months (n=497) Duration of more than 3 months (n=219) p-value Killip class (%) I 409 (82.3) 187 (85.4) II 42 (8.5) 15 (6.8) III 34 (6.8) 8 (3.7) IV 12 (2.4) 9 (4.1) LV ejection fraction, % 55.84± ± LV ejection fraction <50% (%) 137 (28.1) 54 (25.0) Creatinine clearance, ml/min 71.29± ± CKD (Ccr<60) 176 (35.6) 70 (32.3) Chronic kidney disease (%) Stage (21.9) 64 (29.5) Stage (42.5) 83 (38.2) Stage (30.8) 57 (26.3) Stage 4 18 (3.6) 10 (4.6) Stage 5 6 (1.2) 3 (1.4)

20 Angiographic Characteristics according to DTPA of 3-month Duration of less than 3 months (n=497) Duration of more than 3 months (n=219) p-value Infarct-related artery (%) LAD 262 (52.7) 116 (53.0) LCX 71 (14.3) 27 (12.3) RCA 152 (30.6) 72 (32.9) LM 12 (2.4) 5 (1.8) Diseased vessels (%) Single vessel 242 (48.7) 107 (48.9) Two vessel 141 (28.4) 59 (26.9) Three vessel 83 (16.7) 39 (17.8) LM disease 31 (6.2) 14 (6.4) ACC/AHA classification (%) Type A or B1 153 (30.8) 68 (31.1) Type B2 or C 344 (69.2) 151 (68.9) Preprocedural TIMI flow grade (%) (40.6) 98 (44.7) I 22 (4.4) 14 (6.4) II 131 (26.4) 57 (26.0) III 142 (28.6) 50 (22.8) 0.110

21 Procedural Characteristics according to DTPA of 3-month Duration of less than 3 months (n=497) Duration of more than 3 months (n=219) p-value Postprocedural TIMI flow grade (%) (0.4) 0 (0.0) I 0 (0.0) 1 (0.5) II 9 (1.8) 2 (0.9) III 486 (97.8) 216 (98.6) Use of Gp IIb/IIIa inhibitor 175 (35.2) 78 (35.6) Type of stent used (%) TAXUS 354 (71.2) 173 (79.0) Cypher 82 (16.5) 32 (14.6) Endeavor 61 (12.3) 14 (6.4) Stent diameter at target lesion, mm 3.20± ± Stent length at target lesion, mm 25.25± ± Total number of stents 1.73± ±

22 12-month Clinical Outcomes according to DTPA of 3-month Duration of less than 3M Duration of more than 3M p=0.088 p=0.183 p=0.310 p=0.232 p=0.606 p=0.033 p= Cardiac Non-fatal TLR TVR Stent Safety EP MACE death MI thrombosis

23 Bleeding Complications according to DTPA Group I (n=265) Group II (n=232) Group III (n=86) Group IV (n=133) p-value * Degree of bleeding according to TIMI criteria (%) Major 0 (0.0) 1 (0.4) 0 (0.0) 0 (0.0) Minor 3 (1.1) 0 (0.0) 0 (0.0) 0 (0.0) Minimal 3 (1.1) 2 (0.9) 2 (2.3) 1 (0.8) Need for transfusion (%) 20 (7.5) 20 (8.6) 6 (6.4) 7 (5.3) * p-value of the chi-square test for linear trend.

24 Kaplan-Meier MACE Free Survival Curve

25 Independent Predictors of 1-year MACE Variables HR 95.0% C.I. p-values Killip class IV (vs. class I) Triple therapy duration 3 months Current smoker Use of Glycoprotein IIb/IIIa inhibitor ACC/AHA type B2/C lesion History of ischemic heart disease Diagnosed ST elevation MI History of diabetes mellitus Stage 5 CKD (vs. stage 1) Variables: Age, Gender, HTN hx, DM hx, Dyslipidemia hx, Current smoker, Family Hx, IHD hx, STEMI or NSTEMI, Use of Gp IIb/IIIa inhibitor, ACC/AHA type B2/C lesions, LM or 3VD, LVEF, creatinine clearance, Killip class, Type of DES, TA duration more than 3 months

26 Subgroup analyses

27 Limitations It was conducted as a single-center, retrospective nonrandomized comparative study. This might have introduced a significant bias in patient selection, even though it was partially compensated for by multivariate Cox regression model using propensity score to control the baseline biases. There were a little medical records about adverse reactions to cilostazol and why the patients stopped taking the cilostazol.

28 Conclusions Our data shows that longer duration of TA isn t always associated with better clinical outcomes. However, TA duration of more than at least 3 months appears more effective in patients with AMI undergoing DES implantation. The large long-term prospective randomized trials are needed to assess the optimal duration of TAP in AMI patients.

29 Thank you for your attention!